The role of dietary compounds in cancer prevention and treatment has been widely discussed (1-3). In this regard, the potential chemopreventive effect of garlic has been of interest since garlic contains numerous pharmacologically active substances including sulfur and selenocompounds that have been shown to alter the activation of several carcinogens and to inhibit cancer cell growth and/or to induce cell death (4-6). Sulfur compounds such as diallyl sulfide, S-allylmercaptocysteine, and ajoene isolated from garlic have been known to increase the activity of enzymes involved in the metabolism of carcinogens (7) and have anti-oxidant activities (8) and protective activities against lipid peroxidation and hepato toxicity in vitro and in vivo (9, 10).
Several recent studies showed that these sulfur compounds are able to inhibit the growth of several human cancer cells including breast (MCF-7), hepatoma (HepG2), and lymphocytic leukemia as well as lung cancer cells (NSCLC) in culture (11-14). In addition, the importance of sulfur compounds in the preventative effect against colon cancer development has been demonstrated by several research groups (15-17). Jakubikova and Sedlak reported that organosulfides derived from garlic induced apoptotic cell death of human colon carcinoma cell lines (15). Garlic containing sulfur compounds has also been demonstrated to prevent chemical-induced rat aberrant crypt formation (16) and colon cancer incidence (17). Even though sulfur compounds from natural products have been demonstrated as chemopreventive agents, their molecular mechanisms are not fully demonstrated.
Recent evidences indicate that nuclear transcription factor-κB (NF-κB) activation has been connected with multiple aspects of oncogenesis, including the control of apoptosis, proliferation, differentiation, and migration of the cells (18-20). An association of colorectal cancer development and activation of NF-κB has been demonstrated. NF-κB activities were increased in the colon cancer cell lines and human tumor samples as well as nucleic of stromal macropharges in sporadic adenomatous polyps (21, 22). NF-κB can lead to further proliferation of transformed cells through enhanced production of growth factors and cytokines (23). Thus, an inactivation of NF-κB in many cancer cells by a chemotherapeutic agent has been demonstrated to blunt the ability of the cancer cells to grow by the antiapoptotic function of NF-κB in mammalian cells (24-27). Although many compounds have been identified from garlic (28, 29) and their anticancer activities (4-6) have been demonstrated, new compounds and action mechanisms underlying their anticancer effects have been not fully studied.
Throughout this application, various patents and publications are referenced, and citations are provided in parentheses. The disclosure of these patents and publications in their entities are hereby incorporated by reference into this application.